PROJECT SUMMARY In the United States, about 62% of Medicare recipients ages 65 to 74 years have multiple chronic conditions (MCC; ? 2 chronic conditions), and the frequency increases dramatically to 82% above age 85. Because adults with MCC are at increased risk of functional decline and are particularly vulnerable to poor care, MCC threatens both the public and financial health of the United States. MCC prevalence may be reduced by delaying the onset of single conditions and combinations of conditions through modification of risk factors or determinants of diseases. However, current preventive efforts have partly failed because they have focused on one disease at a time and too late in life. For this reason, there is a critical need to identify groups of individuals at risk earlier in life, and to develop interventions to prevent MCC and their adverse health outcomes. These priorities were outlined in the Multiple Chronic Conditions Strategic Framework of the US Department of Health and Human Services (DHHS) of 2010. A growing body of literature has described patterns of prevalent MCC in the United States and worldwide; however, the patterns of incidence of MCC and the outcomes of MCC remain poorly understood. In addition, the National Institute on Aging has recommended the novel approach of considering MCC as a proxy measure (clinical marker) of accelerated aging. Therefore, we will study the incidence and the rate of accumulation of MCC and the health outcomes of MCC across the entire life span. The Rochester Epidemiology Project (REP) is an ideal environment to study the incidence and rate of accumulation of MCC, and the outcomes of MCC because it includes information for all ages from new- borns to death, regardless of insurance status or health care setting, and encompasses the full spectrum of care, from primary to tertiary care. In this application, we propose to study the incidence and life course accumulation of MCC using 18 selected somatic and mental health conditions across all ages (Aim 1), to study the short-term and long-term medical-records-based adverse health outcomes of incident MCC (Aim 2), and to study the short-term and long-term patient reported adverse outcomes of incident MCC (Aim 3). Understanding the incidence and accumulation of MCC, and its objective and subjective health outcomes is critical to enabling clinical and public health agencies to prevent and treat MCC, and to improve population health. In addition, these studies will identify persons at high risk of developing MCC early in life (accelerated aging). These persons may be selected for future studies of biomarkers (e.g., blood tests, genetic tests, imaging) or for preventive interventions to slow aging (e.g., specific drugs, dietary modification, lifestyle modification). Studying MCC as a clinical marker will advance our understanding of aging. In summary, the studies proposed here are novel, can be efficiently conducted using the REP, and are urgently needed.